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Adipocyte fatty acid-binding protein is released from adipocytes by a non-conventional mechanism

International Journal of Obesity volume 38, pages 1251–1254 (2014)Cite this article

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Abstract

Adipocyte fatty acid-binding protein (AFABP) is an adipokine, which induces insulin resistance. However, AFABP does not possess any secretion-directed signals and the mechanisms for AFABP release have not been thoroughly assessed so far. In the current study, mechanisms for AFABP secretion were elucidated in 3T3-L1 adipocytes in vitro in the presence or absence of hormonal stimulation, calcium ionophore and secretion inhibitors by cell fractionation experiments, immunoblotting and ELISAs. We demonstrate that AFABP secretion is upregulated during adipocyte differentiation. AFABP secretion is not influenced by treatment with protein secretion inhibitors that block vesicular traffic at the endoplasmic reticulum and the Golgi apparatus. AFABP is secreted partially by adipocyte-derived microvesicles (ADMs), an established mechanism for unconventional secretion from adipocytes. Both total and ADM-secreted AFABP are downregulated by insulin and upregulated by the calcium ionophore ionomycin. Furthermore, murine RAW 264.7 macrophages secrete AFABP and AFABP release from these cells is upregulated by lipopolysaccharide treatment. Taken together, these results suggest that AFABP is actively released by unconventional mechanisms and by ADMs from 3T3-L1 adipocytes. Furthermore, AFABP secretion from fat cells is regulated by insulin and intracellular calcium.

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Acknowledgements

This study was supported by grants to MF from the Deutsche Forschungsgemeinschaft (DFG, SFB 1052/1, C06), the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (IFB Adiposity Diseases, project K7-3 and K7-58), and the Deutsche Hochdruckliga e.V. Furthermore, TE was supported by a junior research grant by the Medical Faculty, University of Leipzig, and the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (IFB Adiposity Diseases, MetaRot program). We thank Stephan Lorenz for scientific insights and discussion.

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Authors and Affiliations

  1. Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany

    S Kralisch, T Ebert, U Lossner, B Jessnitzer, M Stumvoll & M Fasshauer

  2. IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany

    S Kralisch, T Ebert, U Lossner & M Fasshauer

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  1. S Kralisch
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  2. T Ebert
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  3. U Lossner
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Correspondence to S Kralisch.

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Kralisch, S., Ebert, T., Lossner, U. et al. Adipocyte fatty acid-binding protein is released from adipocytes by a non-conventional mechanism. Int J Obes 38, 1251–1254 (2014). https://doi.org/10.1038/ijo.2013.232

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